Inverse treatment planning for targeted radionuclide therapy

Full text: A method for inverse treatment planning was developed for targeted radionuclide therapy. Taking into account the fact that the efficacy of targeting radionuclide therapy is affected by nonuniformity dose and dose rate distributions in tumors, we introduce the equivalent uniform biologically effective dose (EUBED) concept on treatment planning for targeting radionuclide therapy. The EUBED model converts the spatial biologically effective dose (BED) distribution into an equivalent uniform biologically effective dose value that would produce a biological response similar to that expected from de original BED distribution. According to this, the treatment planning must quantify the relationship between administered activity and the absorbed dose distribution that expressed in terms of biological effect maximizing the EUBED in tumor while the mean dose in dose-limiting normal organs is maintained within accepted values. The method is based on calculation of the absorbed dose distribution using patient-specific imaging data, incorporating radiobiologic modeling to account for effects of dose rate distribution for better prediction of tumor response. For BED calculation, we use a BED model based on cell repair and proliferation during the internal irradiation at low dose rate with beta emitters. The inverse planning process consists in the estimation of activity to be administered from treatment prescription in terms of tumor control probability (TCP), assuming that each amount of administered activity produces the same biological effect, for treatment schemes that uses multiple activity administrations equally time-spaced. From SPECT images of absorbed dose distribution at voxel level in Gy/GBq, the differential dose volume histogram is obtained and used together with the mean absorbed dose of the dose-limiting organ as input parameters. From prescribed TCP, the corresponding EUBED is calculated and divided by the number of activity administrations to determine the partial EUBED for one administration. The amount of activity, that produces an EUBED equals to the previously calculated partial EUBED, is determined by an iterative method, from the differential dose volume histogram (DVH). In this algorithm, the constraint condition is that the estimated amount of activity must be lesser than maximum tolerate activity (MTA) by the dose-limiting organ. The optimization process consist in to maximize the EUBED, while the mean dose to limiting-dose organ is maintained within the accept values varying the number of activity administrations. This process is based on the fact that in presence of nonuniform dose distribution, the treatment is less effective as the activity increase and the dose fractionation is better tolerated by patients and may help to alleviate the effects of nonuniform dose distribution on treatment efficacy. The method was validated using a clinical case data for different treatment schemes with different numbers of equal amount of administered activity. The total activity was the same for each selected treatment scheme from which the TCP was estimated by direct treatment planning from SPECT images. Because of, the DVH comprise in one single graph the spatial absorbed dose distribution, the results of inverse treatment planning using the TCP obtained from direct planning were compared with the results of direct planning. The comparison showed no significant differences for both methods. These results validate the method of inverse planning dosimetry proposed in this work. The obtained results also were compared with the treatment planning based on mean BED to explore the impact of nonuniform BED distribution on treatment efficacy. This analysis demonstrates an important reduction on achieved EUBED for each selected treatment scheme which contribute to reduce the therapeutic effect. A more detailed description of the method will be published elsewhere. The inverse treatment planning is useful for estimation of the amount of activity to produce an expected effect in terms of prescribed TCP for treatment schemes based on multiple activity administrations and could be applied in clinical routine if radiobiologic parameters of tumor are available. The analysis of results of treatment planning based on mean BED shows an important reduction of likelihood to achieve the tumor control when dose distribution is nonuniform